tbuckley/cabot-search huggingface dataset:
Distinct use of super-enhancer elements controls cell type–specific CD25 transcription and function
Authors: Rosanne Spolski, Peng Li, Vivek Chandra, Boyoung Shin, Shubham Goel, Keiko Sakamoto, Chengyu Liu, Jangsuk Oh, Min Ren, Yutaka Enomoto, Erin E. West, Stephen M. Christensen, Edwin C. K. Wan, Meili Ge, Jian-Xin Lin, Bingyu Yan, Majid Kazemian, Zu-Xi Yu, Keisuke Nagao, Pandurangan Vijayanand, Ellen V. Rothenberg, Warren J. Leonard
Journal: Science Immunology (2023)

The IL-2 receptor α chain (IL-2Rα/CD25) is constitutively expressed on double-negative (DN2/DN3 thymocytes and regulatory T cells (T regs ) but induced by IL-2 on T and natural killer (NK) cells, with Il2ra expression regulated by a STAT5-dependent super-enhancer. We investigated CD25 regulation and function using a series of mice with deletions spanning STAT5-binding elements. Deleting the upstream super-enhancer region mainly affected constitutive CD25 expression on DN2/DN3 thymocytes and T regs , with these mice developing autoimmune alopecia, whereas deleting an intronic region decreased IL-2–induced CD25 on peripheral T and NK cells. Thus, distinct super-enhancer elements preferentially control constitutive versus inducible expression in a cell type–specific manner. The mediator-1 coactivator colocalized with specific STAT5-binding sites. Moreover, both upstream and intronic regions had extensive chromatin interactions, and deletion of either region altered the super-enhancer structure in mature T cells. These results demonstrate differential functions for distinct super-enhancer elements, thereby indicating previously unknown ways to manipulate CD25 expression in a cell type–specific fashion.
The Acute Effects of Real-World Physical Activity on Glycemia in Adolescents With Type 1 Diabetes: The Type 1 Diabetes Exercise Initiative Pediatric (T1DEXIP) Study
Authors: Michael C. Riddell, Robin L. Gal, Simon Bergford, Susana R. Patton, Mark A. Clements, Peter Calhoun, Lindsey C. Beaulieu, Jennifer L. Sherr
Journal: Diabetes Care (2023)

Data from the Type 1 Diabetes Exercise Initiative Pediatric (T1DEXIP) study were evaluated to understand glucose changes during activity and identify factors that may influence changes.In this real-world observational study, adolescents with type 1 diabetes self-reported physical activity, food intake, and insulin dosing (multiple-daily injection users) using a smartphone application. Heart rate and continuous glucose monitoring data were collected, as well as pump data downloads.Two hundred fifty-one adolescents (age 14 ± 2 years [mean ± SD]; HbA1c 7.1 ± 1.3% [54 ± 14.2 mmol/mol]; 42% female) logged 3,738 activities over ∼10 days of observation. Preactivity glucose was 163 ± 66 mg/dL (9.1 ± 3.7 mmol/L), dropping to 148 ± 66 mg/dL (8.2 ± 3.7 mmol/L) by end of activity; median duration of activity was 40 min (20, 75 [interquartile range]) with a mean and peak heart rate of 109 ± 16 bpm and 130 ± 21 bpm. Drops in glucose were greater in those with lower baseline HbA1c levels (P = 0.002), shorter disease duration (P = 0.02), less hypoglycemia fear (P = 0.04), and a lower BMI (P = 0.05). Event-level predictors of greater drops in glucose included self-classified "noncompetitive" activities, insulin on board >0.05 units/kg body mass, glucose already dropping prior to the activity, preactivity glucose >150 mg/dL (>8.3 mmol/L) and time 70-180 mg/dL >70% in the 24 h before the activity (all P < 0.001).Participant-level and activity event-level factors can help predict the magnitude of drop in glucose during real-world physical activity in youth with type 1 diabetes. A better appreciation of these factors may improve decision support tools and self-management strategies to reduce activity-induced dysglycemia in active adolescents living with the disease.
A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization
Authors: Zhengzi Yi, Caixia Xi, Madhav C. Menon, Paolo Cravedi, Fasika Tedla, Alan Soto, Zeguo Sun, Keyu Liu, Jason Zhang, Chengguo Wei, Man Chen, Wenlin Wang, Brandon Veremis, Monica Garcia-barros, Abhishek Kumar, Danielle Haakinson, Rachel Brody, Evren U. Azeloglu, Lorenzo Gallon, Philip O’Connell, Maarten Naesens, Ron Shapiro, Robert B. Colvin, Stephen Ward, Fadi Salem, Weijia Zhang
Journal: Kidney International (2023)
Diabetes Distress and Associations With Demographic and Clinical Variables: A Nationwide Population-Based Registry Study of 10,186 Adults With Type 1 Diabetes in Norway
Authors: Ingvild Hernar, John G. Cooper, Roy M. Nilsen, Timothy C. Skinner, Ragnhild B. Strandberg, Marjolein M. Iversen, Marit Graue, Tony Ernes, Karianne F. Løvaas, Tone V. Madsen, Silje S. Lie, David A. Richards, Grethe Å. Ueland, Anne Haugstvedt
Journal: Diabetes Care (2023)

OBJECTIVE To estimate diabetes distress prevalence and associations with demographic and clinical variables among adults with type 1 diabetes in Norway. RESEARCH DESIGN AND METHODS In this nationwide population-based registry study, the 20-item Problem Areas in Diabetes (PAID-20) questionnaire was sent to 16,255 adults with type 1 diabetes. Linear regression models examined associations of demographic and clinical variables with distress. RESULTS In total, 10,186 individuals (62.7%) completed the PAID-20, with a mean score of 25.4 (SD 18.4) and 21.7% reporting high distress. Respondents endorsed worrying about the future and complications as the most problematic item (23.0%). Female sex, younger age, non-European origin, primary education only, unemployment, smoking, continuous glucose monitoring use, more symptomatic hypoglycemia, reduced foot sensitivity, treated retinopathy, and higher HbA1c were associated with higher distress. CONCLUSIONS Diabetes distress is common among adults with type 1 diabetes and associated with clinically relevant factors, underlining that regular care should include efforts to identify and address distress.
Sociodemographic characteristics and longitudinal progression of multimorbidity: A multistate modelling analysis of a large primary care records dataset in England
Authors: Sida Chen, Tom Marshall, Christopher Jackson, Jennifer Cooper, Francesca Crowe, Krish Nirantharakumar, Catherine L. Saunders, Paul Kirk, Sylvia Richardson, Duncan Edwards, Simon Griffin, Christopher Yau, Jessica K. Barrett
Journal: PLoS Medicine (2023)

Multimorbidity, characterised by the coexistence of multiple chronic conditions in an individual, is a rising public health concern. While much of the existing research has focused on cross-sectional patterns of multimorbidity, there remains a need to better understand the longitudinal accumulation of diseases. This includes examining the associations between important sociodemographic characteristics and the rate of progression of chronic conditions.
Ramadan intermittent fasting and its association with health-related indices and exercise test performance in athletes and physically active individuals: an overview of systematic reviews
Authors: Khaled Trabelsi, Achraf Ammar, Omar Boukhris, Mohamed Ali Boujelbane, Cain Clark, Mohamed Romdhani, Jad Adrian Washif, Abdul Rashid Aziz, Nicola Luigi Bragazzi, Jordan M Glenn, Karim Chamari, Hamdi Chtourou, Haitham Jahrami
Journal: British Journal of Sports Medicine (2023)

Objective To systematically review, summarise and appraise findings of published systematic reviews, with/without meta-analyses, examining associations between Ramadan fasting observance (RO), health-related indices and exercise test performances in athletes and physically active individuals. Design Overview of systematic reviews with assessment of reviews’ methodological quality. Data sources PubMed, Web of Science, Scopus, Cochrane Database of Systematic Reviews, SPORTDiscus, ProQuest, PsycINFO and SciELO. Eligibility criteria for selecting studies Systematic reviews with/without meta-analyses examining associations of RO with health-related indices and exercise performances in athletes and physically active individuals. Results Fourteen systematic reviews (seven with meta-analyses) of observational studies, with low-to-critically-low methodological quality, were included. Two reviews found associations between RO and decreased sleep duration in athletes and physically active individuals. One review suggested athletes may experience more pronounced reductions in sleep duration than physically active individuals. One review found associations between RO and impaired sleep quality in athletes and physically active individuals. RO was associated with decreased energy, carbohydrate and water intake in adult-aged athletes, but not adolescents. One review suggests RO was associated with athletes’ increased feelings of fatigue and decreased vigour. No association was found between RO and athletes’ lean mass or haematological indices. RO was unfavourably associated with changes in athletes’ performance during high-intensity exercise testing. Conclusion Continuance of training during RO could be associated with athletes’ mood state disturbances, decreased sleep duration and performance decline during high-intensity exercise testing, while preserving lean mass. However, careful interpretation is necessary due to the low-to-critically-low methodological quality of the included reviews.
Biopolymer‐Assembled Porous Hydrogel Microfibers from Microfluidic Spinning for Wound Healing
Authors: Yu Wang, Jiahui Guo, Zhiqiang Luo, Yingbo Shen, Jinglin Wang, Yunru Yu, Yuanjin Zhao
Journal: Advanced Healthcare Materials (2023)

Hydrogels are considered as a promising medical patch for wound healing. Researches in this aspect are focused on improving their compositions and permeability to enhance the effectiveness of wound healing. Here, novel prolamins-assembled porous hydrogel microfibers with the desired merits for treating diabetes wounds are presented. Such microfibers are continuously generated by one-step microfluidic spinning technology with acetic acid solution of prolamins as the continuous phase and deionized water as the dispersed phase. By adjusting the prolamin concentration and flow rates of microfluidics, the porous structure and morphology as well as diameters of microfibers can be well tailored. Owing to their porosity, the resultant microfibers can be employed as flexible delivery systems for wound healing actives, such as bacitracin and vascular endothelial growth factor (VEGF). It is demonstrated that the resultant hydrogel microfibers are with good cell-affinity and effective drug release efficiency, and their woven patches display superior in vivo capability in treating diabetes wounds. Thus, it is believed that the proposed prolamins-assembled porous hydrogel microfibers will show important values in clinic wound treatments.
Political Ideology and Trust in Government Health Agencies for Cancer Information
Authors: Onyema G. Chido-Amajuoyi, Henry K. Onyeaka, Itunu O. Sokale, Somto Nwani, Carlos H. Barcenas, Hermioni L. Amonoo, Sanjay Shete
Journal: JAMA Network Open (2023)

This cross-sectional study assesses the association between political ideology and trust in government health agencies for cancer information.
Sleep Disturbance and Burnout in Emergency Department Health Care Workers
Authors: Ari Shechter, Tsion Firew, Maody Miranda, Nakesha Fray, Allison A. Norful, Alvis Gonzalez, Bernard P. Chang
Journal: JAMA Network Open (2023)

This cross-sectional study examines the association of sleep disturbances with burnout among emergency medicine health care workers.
Cost-Effectiveness of Pharmacist Prescribing for Managing Hypertension in the United States
Authors: Dave L. Dixon, Karissa Johnston, Julie Patterson, Carlo A. Marra, Ross T. Tsuyuki
Journal: JAMA Network Open (2023)

Pharmacist-led interventions can significantly improve blood pressure (BP) control. The long-term cost-effectiveness of pharmacist-prescribing interventions implemented on a large scale in the US remains unclear.
Teleworking, Parenting Stress, and the Health of Mothers and Fathers
Authors: John James Parker, Craig F. Garfield, Clarissa D. Simon, Anne Bendelow, Marie E. Heffernan, Matthew M. Davis, Kristin Kan
Journal: JAMA Network Open (2023)

This cross-sectional study examines the associations of telework during the COVID-19 pandemic with parents’ general health, changes to mental health, and parenting stress.
Use of Dexmedetomidine and Opioids in Hospitalized Preterm Infants
Authors: Samantha Curtis, Ryan Kilpatrick, Zeenia C. Billimoria, Kanecia Zimmerman, Veeral Tolia, Reese Clark, Rachel G. Greenberg, Mihai Puia-Dumitrescu
Journal: JAMA Network Open (2023)

Importance Dexmedetomidine, an α 2 -adrenergic agonist, is not approved by the Food and Drug Administration for use in premature infants. However, the off-label use of dexmedetomidine in premature infants has increased 50-fold in the past decade. Currently, there are no large studies characterizing dexmedetomidine use in US neonatal intensive care units (NICUs) or comparing the use of dexmedetomidine vs opioids in infants. Objectives To describe dexmedetomidine use patterns in the NICU and examine the association between dexmedetomidine and opioid use in premature infants. Design, Setting, and Participants A multicenter, observational cohort study was conducted from November 11, 2022, to April 4, 2023. Participants were inborn infants born between 22 weeks, 0 days, and 36 weeks, 6 days, of gestation at 1 of 383 Pediatrix Medical Group NICUs across the US between calendar years 2010 and 2020. Main Outcome and Measure Exposure to medications of interest defined as total days of exposure, timing of use, and changes over time. Results A total of 395 122 infants were included in the analysis. Median gestational age was 34 (IQR, 32-35) weeks, and median birth weight was 2040 (IQR, 1606-2440) g. There were 384 infants (0.1% of total; 58.9% male) who received dexmedetomidine. Infants who received dexmedetomidine were born more immature, had lower birth weight, longer length of hospitalization, more opioid exposure, and more days of mechanical ventilation. Dexmedetomidine use increased from 0.003% in 2010 to 0.185% in 2020 ( P &amp;amp;lt; .001 for trend), while overall opioid exposure decreased from 8.5% in 2010 to 7.2% in 2020 ( P &amp;amp;lt; .001 for trend). The median postmenstrual age at first dexmedetomidine exposure was 31 (IQR, 27-36) weeks, and the median postnatal age at first dexmedetomidine exposure was 3 (IQR, 1-35) days. The median duration of dexmedetomidine receipt was 6 (IQR, 2-14) days. Conclusion and Relevance The findings of this multicenter cohort study of premature infants suggest that dexmedetomidine use increased significantly between 2010 and 2020, while overall opioid exposure decreased. Future studies are required to further examine the short- and long-term effects of dexmedetomidine in premature and critically ill infants.
Antibody Drug Clearance: An Underexplored Marker of Outcomes with Checkpoint Inhibitors
Authors: Yizhen Guo, Bryan C. Remaily, Justin Thomas, Kyeongmin Kim, Samuel K. Kulp, Thomas A. Mace, Latha P. Ganesan, Dwight H. Owen, Christopher C. Coss, Mitch A. Phelps
Journal: Clinical Cancer Research (2023)

Abstract Immune-checkpoint inhibitor (ICI) therapy has dramatically changed the clinical landscape for several cancers, and ICI use continues to expand across many cancer types. Low baseline clearance (CL) and/or a large reduction of CL during treatment correlates with better clinical response and longer survival. Similar phenomena have also been reported with other monoclonal antibodies (mAb) in cancer and other diseases, highlighting a characteristic of mAb clinical pharmacology that is potentially shared among various mAbs and diseases. Though tempting to attribute poor outcomes to low drug exposure and arguably low target engagement due to high CL, such speculation is not supported by the relatively flat exposure–response relationship of most ICIs, where a higher dose or exposure is not likely to provide additional benefit. Instead, an elevated and/or increasing CL could be a surrogate marker of the inherent resistant phenotype that cannot be reversed by maximizing drug exposure. The mechanisms connecting ICI clearance, therapeutic efficacy, and resistance are unclear and likely to be multifactorial. Therefore, to explore the potential of ICI CL as an early marker for efficacy, this review highlights the similarities and differences of CL characteristics and CL-response relationships for all FDA-approved ICIs, and we compare and contrast these to selected non-ICI mAbs. We also discuss underlying mechanisms that potentially link mAb CL with efficacy and highlight existing knowledge gaps and future directions where more clinical and preclinical investigations are warranted to clearly understand the value of baseline and/or time-varying CL in predicting response to ICI-based therapeutics.
Analysis of the Breast Cancer Journey in Namibia
Authors: Pauline Boucheron, Annelle Zietsman, Johanna Pontac, Rolf Hansen, Benjamin O. Anderson, Kayo Togawa, Peter M. Macharia, Milena Foerster, Joachim Schüz, Isabel dos-Santos-Silva, Valerie McCormack
Journal: JAMA Network Open (2023)

Importance Breast cancer (BC) is the leading cancer among women in Namibia. Examining the BC journey in this multiracial country where inequalities remain large is needed to inform effective interventions to reduce BC mortality. Objective To describe the entire BC journey of Namibian women by race, utilizing the World Health Organization Global Breast Cancer Initiative (GBCI) framework. Design, Setting, and Participants This cohort study used the Namibian subset of the African Breast Cancer–Disparities in Outcomes prospective cohort. Participants were all Namibian residents with confirmed incident BC who presented at the main national public oncology center of the Windhoek Central Hospital (WCH). Follow-up started from recruitment (September 8, 2014, to October 5, 2016) and ended up to 3 years after diagnosis (December 13, 2014, to September 27, 2019). Data analysis was conducted from June 2022 to August 2023. Exposures Participants’ self-reported ethnicities were aggregated into 3 population groups: Black, mixed ancestry, and White. Main Outcomes and Measures Three-year overall survival (OS) was examined using Cox models, and summary statistics were used to describe women’s BC journey, including GBCI pillar key performance indicators: (1) early stage (TNM I or II) diagnosis (population benchmark ≥60%), (2) prompt diagnosis, ie, 60 days or less to first health care practitioner visit (population benchmark 100%), and (3) completion of recommended multimodal treatment (MT, ie, surgery plus chemotherapy) (population benchmark ≥80%). Results Of 405 women, there were 300 (74%) Black (mean [SD] age, 53 [15] years), 49 (12%) mixed ancestry (mean [SD] age, 53 [7] years), and 56 (14%) White (mean [SD] age, 59 [12] years) patients. Three-year OS was lowest in Black women (60% [95% CI, 54%-66%]; mixed ancestry: 80% [95% CI, 65%-89%]; White: 89% [95% CI, 77%-95%]), who had lower prevalence of early stage diagnosis (Black: 37% [95% CI, 31%-42%]; mixed ancestry and White: 75% [95% CI, 66%-83%]) and timely diagnosis (Black: 60% [95% CI, 54%-66%]; mixed ancestry and White: 77% [95% CI, 69%-85%]), while MT completion (Black: 53% [95% CI, 46%-59%]; mixed ancestry and White: 63% [95% CI, 50%-73%]) was low in all women. Conclusions and Relevance In this cohort study of 405 Namibian residents with BC, marked racial disparities in survival were paralleled by inequities all along the BC journey. To improve BC survival, interventions are needed to promote earlier diagnosis in Black Namibian women and to increase MT initiation and completion in all women.
Fairness of Machine Learning Algorithms for Predicting Foregone Preventive Dental Care for Adults
Authors: Helena Silveira Schuch, Mariane Furtado, Gabriel Ferreira dos Santos Silva, Ichiro Kawachi, Alexandre D. P. Chiavegatto Filho, Hawazin W. Elani
Journal: JAMA Network Open (2023)

Importance Access to routine dental care prevents advanced dental disease and improves oral and overall health. Identifying individuals at risk of foregoing preventive dental care can direct prevention efforts toward high-risk populations. Objective To predict foregone preventive dental care among adults overall and in sociodemographic subgroups and to assess the algorithmic fairness. Design, Setting, and Participants This prognostic study was a secondary analyses of longitudinal data from the US Medical Expenditure Panel Survey (MEPS) from 2016 to 2019, each with 2 years of follow-up. Participants included adults aged 18 years and older. Data analysis was performed from December 2022 to June 2023. Exposure A total of 50 predictors, including demographic and socioeconomic characteristics, health conditions, behaviors, and health services use, were assessed. Main Outcomes and Measures The outcome of interest was foregoing preventive dental care, defined as either cleaning, general examination, or an appointment with the dental hygienist, in the past year. Results Among 32 234 participants, the mean (SD) age was 48.5 (18.2) years and 17 386 participants (53.9%) were female; 1935 participants (6.0%) were Asian, 5138 participants (15.9%) were Black, 7681 participants (23.8%) were Hispanic, 16 503 participants (51.2%) were White, and 977 participants (3.0%) identified as other (eg, American Indian and Alaska Native) or multiple racial or ethnic groups. There were 21 083 (65.4%) individuals who missed preventive dental care in the past year. The algorithms demonstrated high performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.84 (95% CI, 0.84-0.85) in the overall population. While the full sample model performed similarly when applied to White individuals and older adults (AUC, 0.88; 95% CI, 0.87-0.90), there was a loss of performance for other subgroups. Removing the subgroup-sensitive predictors (ie, race and ethnicity, age, and income) did not impact model performance. Models stratified by race and ethnicity performed similarly or worse than the full model for all groups, with the lowest performance for individuals who identified as other or multiple racial groups (AUC, 0.76; 95% CI, 0.70-0.81). Previous pattern of dental visits, health care utilization, dental benefits, and sociodemographic characteristics were the highest contributing predictors to the models’ performance. Conclusions and Relevance Findings of this prognostic study using cohort data suggest that tree-based ensemble machine learning models could accurately predict adults at risk of foregoing preventive dental care and demonstrated bias against underrepresented sociodemographic groups. These results highlight the importance of evaluating model fairness during development and testing to avoid exacerbating existing biases.
Factors Associated With Abrupt Discontinuation of Long-Term High-Dose Opioid Treatment
Authors: Carolina Vivas-Valencia, Huiru Dong, Erin J. Stringfellow, W. Alton Russell, Jake R. Morgan, Mina Tadrous, Mohammad S. Jalali
Journal: JAMA Network Open (2023)

This cohort study investigates factors associated with abrupt discontinuation of long-term high-dose opioid treatment at the national level and across US states.